The aim of this study was to explore the associations between diet quality, socio-demographic measures, smoking, and weight status in a large, cross-sectional cohort of adults living in Yorkshire and Humber, UK. Data from 43, 023 participants aged over 16 years in the Yorkshire Health Survey, 2nd wave (2013–2015) were collected on diet quality, socio-demographic measures, smoking, and weight status. Diet quality was assessed using a brief, validated tool. Associations between these variables were assessed using multiple regression methods. Split-sample cross-validation was utilised to establish model portability. Observed patterns in the sample showed that the greatest substantive differences in diet quality were between females and males (3.94 points; P < 0.001) and non-smokers vs smokers (4.24 points; P < 0.001), with higher diet quality scores observed in females and non-smokers. Deprivation, employment status, age, and weight status categories were also associated with diet quality. Greater diet quality scores were observed in those with lower levels of deprivation, those engaged in sedentary occupations, older people, and those in a healthy weight category. Cross-validation procedures revealed that the model exhibited good transferability properties. Inequalities in patterns of diet quality in the cohort were consistent with those indicated by the findings of other observational studies. The findings indicate population subgroups that are at higher risk of dietary-related ill health due to poor quality diet and provide evidence for the design of targeted national policy and interventions to prevent dietary-related ill health in these groups. The findings support further research exploring inequalities in diet quality in the population.